Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Department of Oncology Pathology, Cancer Centrum Karolinska, Karolinska Institutet, Stockholm, Sweden.
Neuroscience. 2019 May 1;405:92-102. doi: 10.1016/j.neuroscience.2017.10.034. Epub 2017 Nov 1.
Brain injury is associated with neuroinflammation, and microglia are key players in this process. Microglia can acquire pro-inflammatory or anti-inflammatory properties, but how this affects neural stem cells (NSCs) remains controversial. Here, NSCs were grown in conditioned media collected from either non-stimulated microglia, or microglia stimulated with pro- or anti-inflammatory agents. NSC survival, proliferation, migration, and differentiation were investigated thereafter. We found that NSCs kept in conditioned medium from the anti-inflammatory microglial subtype had better survival, increased migration, and lower astrocytic differentiation compared to NSCs grown in conditioned medium collected from the pro-inflammatory subtype. Finally, we found that NSCs differentiated in microglial conditioned media generated cells expressing the pro-inflammatory chemokine CCL2, most pronounced when differentiated in medium from the pro-inflammatory microglia subtype. Our results show that microglial subtypes regulate NSCs differently and induce generation of cells with inflammatory properties.
脑损伤与神经炎症有关,小胶质细胞是这一过程中的关键角色。小胶质细胞可以获得促炎或抗炎特性,但这如何影响神经干细胞(NSC)仍存在争议。在这里,将 NSC 培养在从小胶质细胞或用促炎或抗炎剂刺激的小胶质细胞收集的条件培养基中。随后研究了 NSC 的存活、增殖、迁移和分化。我们发现,与在促炎亚型收集的条件培养基中培养的 NSC 相比,保存在抗炎小胶质细胞亚型的条件培养基中的 NSC 具有更好的存活能力、更高的迁移能力和更低的星形胶质细胞分化。最后,我们发现,在小胶质细胞条件培养基中分化的 NSC 产生表达促炎趋化因子 CCL2 的细胞,在从促炎小胶质细胞亚型收集的培养基中分化时最为明显。我们的研究结果表明,小胶质细胞亚型以不同的方式调节 NSC,并诱导产生具有炎症特性的细胞。